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        • SCIE

          No association of LCT-13910 single nucleotide polymorphism with gastroenteritis in Korean children

          Choi, Byung Joon,Yoon, Jung Hwan,Choi, Yoo Jin,Han, Lin,Park, Yong Gyu,Park, Won Sang 대한독성유전단백체학회 2013 Molecular & cellular toxicology Vol.9 No.1

          Zinc and lactase deficiency are closely associated with the severity of gastroenteritis in children. Absorption of lactose is dependent on lactase and enhances the absorption of zinc. In the present study, we analyzed the association of the lactase (LCT)-13910 polymorphism and serum zinc levels with the severity of gastroenteritis in Korean children. 133 gastroenteritis patients and 476 healthy controls were examined for their LCT-13910 genotype using a polymerase chain reaction-restriction fragment length polymorphism. We also analyzed serum zinc levels in 111 pediatric patients and compared their severity of gastroenteritis. For the LCT-13910 genotype, all of 133 gastroenteritis patients and 476 healthy children had only the C/C genotype, which is associated with lactase deficiency. In addition, 111 pediatric patients showed no deficit of serum zinc and no association with severity of gastroenteritis. These results suggested that LCT-13910 polymorphism and zinc deficit may not be risk factors and that zinc administration may not be needed in Korean pediatric patients with gastroenteritis.

        • SCIE

          Assessment of human biomonitoring and DNA microarray analysis in the vicinity population on an industrial complex

          Lee, Kyoung-Ho,Chung, Eun-Kyung,Moon, Jeong-Suk,Nam, Suk-Woo,Lee, Mi-Young,Son, Bu-Soon 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.3

          The purpose of this study was to assess current exposure of the population living in the Gwangyang industrial complex and other areas to heavy metals and, VOCs and to identify individual factors associated with urinary and blood levels of these chemicals. The study population was made up of 810 participants ranging in age from 7 to 87 years old at Gwangyang bay in the South Korea. The selected biomarkers represent the main agents to which a population like that of Korean is exposed every day, including 4 heavy metals in blood or urine (Pb in blood and As, Cd, Hg in urine), and VOCs in blood descriptive data analysis leads to mean concentrations of heavy metals, As, Cd, Hg and Pb of 7.34 ${\mu}g$/g cr, 1.04 g/g cr, 1.33 ${\mu}g$/g cr and 2.53 ${\mu}g$/dL, respectively. The mean concentration of benzene, ethylbenzene, tetrachloroehylene, toluene, m-/p-xylene and o-xylene in blood were 0.00 ${\mu}g$/L, 0.00 ${\mu}g$/L, 0.00 ${\mu}g$/L, 0.03 ${\mu}g$/L, 0.00 ${\mu}g$/L and 0.00 ${\mu}g$/L, respectively. The DNA microarray analysis using blood of 16 participants, control group (n=6) and sample group (n=10), showed that the two groups might belong to a different group through hierarchical clustering the present study provides reference values for selected pollutants for the general population in industrial complexes, which can be used for comparison purposes in further studies, since they are mostly within the reference ranges reported by other biomonitoring studies therefore, it would be possible to devise standards for identifying the environmental pollution and beforehand forecast. In addition, it will be the one of the scientific method to help reduce anxiety of residents lived in the polluted areas.

        • SCIE

          Comparative study of active and inactive hepatocarcinogens using a QSAR-based prediction model

          Kang, Jin Seok,Kang, Sukmo,Ryu, Doug-Young,Lee, Yun-Seok,Lee, Jong Kwon,Kang, Tae Seok,Park, Han-Jin,Yoon, Seokjoo 대한독성유전단백체학회 2012 Molecular & cellular toxicology Vol.8 No.4

          In this study, we investigated global gene expression in primary rat hepatocytes treated with three active hepatocarcinogens (prednisolone, dehydroepiandrosterone and monocrotaline), three inactive hepatocarcinogens (hydrocortisone, glycyrrhetinic acid and lithocholic acid) and two unclassified chemicals (griseofulvin (possibly active) and prednisone (possibly inactive)). At 48 h after treatment with these eight chemicals, cells were harvested for RNA extraction. Global gene expression analyses were conducted using oligonucleotide microarrays to detect genes whose expression was altered. Differentially expressed genes (DEG) analysis, principal component analysis (PCA), gene set enrichment analysis (GSEA) and KEGG pathway analysis were also conducted. Seven-hundred and sixty genes whose expression was altered >1.2-fold (P<0.05; unpaired Welch's t-test) were identified as DEGs for the active and inactive carcinogens. In PCA, prednisolone and dehydroepiandrosterone were located away from the inactive carcinogens. In contrast, monocrotaline was close to the inactive carcinogens. Hydrocortisone, glycyrrhetinic acid and lithocholic acid were separate from the active carcinogens. PCA identified griseofulvin as an active carcinogen and prednisone as an inactive carcinogen. GSEA detected several genes associated with hepatocarcinogenesis, such as glutathione S-transferase A2 and NADPH oxidase. KEGG pathway analysis showed that several pathways might be associated with hepatocarcinogenesis. Our results suggest that it may be feasible to differentiate active and inactive hepatocarcinogens by PCA, GSEA and KEGG pathway analysis.

        • SCIE

          Effect of ${\alpha},{\beta}$-unsaturated aldehydes on endothelial cell growth in bacterial cellulose for vascular tissue engineering

          Jeong, Seong Il,Lee, Seung Eun,Yang, Hana,Park, Cheung-Seog,Jin, Young-Ho,Park, Yong Seek 대한독성유전단백체학회 2012 Molecular & cellular toxicology Vol.10 No.1

          Cardiovascular disease is the leading global cause of death. Cigarette smoking is a major risk factor for cardiovascular disease. And ${\alpha},{\beta}$-unsaturated aldehydes such as acrolein and crotonaldehyde are major component of cigarette smoke. Use of replacement grafts materials is one of the cardiovascular disease treatments. However, currently available synthetic materials generally produce poor outcomes including hyperplasia and thrombogenicity. Recently, bacterial synthesized cellulose has received interest as a new functional vascular graft biomaterial owing to its biocompatibility. However, the association of a bacterial cellulose-based scaffold and cigarette smoke is not known. The present study investigated the alteration of function of human umbilical vein endothelial cells (HUVECs) treated with ${\alpha},{\beta}$-unsaturated aldehyde on bacterial cellulose-based material. The data suggest that ${\alpha},{\beta}$-unsaturated aldehydes in cigarette smoke induce altered endothelial cell functions including morphology, adhesion, proliferation, viability and growth on bacterial cellulose. These results may provide the view that cigarette smoking of cardiovascular disease patients applied to bacterial cellulose-based vascular grafts is risk.

        • SCIE

          Sensitizing effect of silencing Ape1/Ref-1 on doxorubicin-induced apoptosis in human carcinoma cells

          Koedrith, Preeyaporn,Seo, Young-Rok 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.4

          Ape1/Ref-1 is a multifunctional protein with major functions in DNA base excision repair system and redox regulation of several transcription factors. However, overexpression of Ape1/Ref-1 is observed in many types of malignant cancers, leading to point that this protein might be a molecular candidate for anticancer drug treatment. A doxorubicin (DOX) has been widely applied in the chemotherapy of solid tumors including lung. Cytotoxification of DOX is targeting on damage to cellular components, particularly DNA molecules, via generation of reactive oxygen species (ROS). Using specific suppression by short hairpin RNA (shRNA)-based viral vector, an important role of Ape1/Ref-1 on DOX resistance in human lung cancer H1299 cell was investigated in this study. Our data revealed that the stable Ape1/Ref-1 shRNA knockdown had higher susceptibility to DOX compared to the wild type. In accordance, intracellular ROS level was notably accelerated in the Ape1/Ref-1 shRNA defect rather than the wild type. Strikingly, our observation represented that in presence of DOX Ape1/Ref-1 deficiency probably stimulated double strand breaks to DNA, detected by neutral comet assay and gamma-H2AX immunoassay, sensitive methods of genotoxicity. Furthermore, our result showed that DOX-induced apoptosis was also correlated with increase in oxygen radicals-generated damage to DNA. We can conclude that Ape1/Ref1-targeted silencing via shRNA-based interference might be a promising molecular strategy to improve effectiveness of DOX-induced apoptosis in treatment of human lung cancer cells, through induction of oxidative insult. This emphasizes that Ape1/Ref-1 might be a prominent therapeutic target in cancer therapy.

        • SCIE

          Identification of estrogenic genes responding to phthalate esters treatment in human MCF-7 cells

          Kim, Youn-Jung,Kim, Eun-Young,Ryu, Jae-Chun 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.2

          The phthalate esters represent a class of chemicals used widely and diversely in industries as a plasticizer for elasticity and adhesion. Some phthalate diesters are classified as endocrine disrupting chemicals (EDCs), because they have been found weakly estrogenic. This study aimed to identify the changes of gene expression profiles by BBP, DBP, and DEHP using cDNA microarray. Firstly, we have selected the MCF-7 cell line, mainly used to estrogenic related research and selected the doses appearing the highest estrogenicity in E-screen assay to examine the estrogenicity and gene expression profiles of phthalate esters. Total RNA was isolated from cells treated with each phthalate esters (BBP, DBP, and DEHP) and $17{\beta}$-estradiol, and then changes of gene expression were analyzed using cDNA microarray (KISTCHIP-400). This microarray includes 416 endocrine related genes based on public database and research papers. For the microarray analysis, genes that showed a 1.5-fold or greater change in their expression level (increase or decrease) were detected as differentially expressed genes (DEGs). Of the 416 genes analyzed, 95, 26, and 63 genes were identified showing significant changes in gene expression resulting from BBP, DBP, and DEHP, respectively. Among these genes, 11 genes, including MGP, SEPP1, and BAK1 were induced by more than 2 of 3 phthalate esters compared with $17{\beta}$-estradiol. Therefore, it suggests that these genes may be associated with estrogenic effect of the phthalate esters on transcriptional level.

        • SCIE

          Expression profiling of liver in Java medaka fish exposed to $17{\beta}$-estradiol

          Woo, Seon-Ock,Jeon, Hye-Young,Lee, Taek-Kyun,Kim, Seong-Ryul,Lee, Seung-Hoon,Yum, Seung-Shic 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.3

          Java medaka ($Oryzias$ $javanicus$) cDNA array was constructed and the microarray platform was used to compare the hepatic expression profiles of Java medaka fish exposed to $17{\beta}$-estradiol with those of unexposed controls. Data analysis demonstrated that the expression profiles were strongly affected by $17{\beta}$-estradiol exposure, with 655 genes up- or downregulated after 24 h, and 633 genes after 48 h. The differentially expressed genes were analyzed to determine the effects of $17{\beta}$-estradiol exposure on the liver tissue and were classified into five functional categories: information storage and processing, cellular processes and signaling, metabolism, general function prediction only, and function unknown. Genes whose expression was upregulated more than 10-fold were predominantly associated with energy production/conversion and reproduction, and 30% of the genes whose expression was downregulated more than 10-fold were associated with carbohydrate transport and metabolism. The observed differences in the expression profiles of 7 genes (encoding apolipoprotein B, cytochrome P450 1A, glucose-6-phosphate dehydrogenase, glutamate dehydrogenase 1b, vitellogenin, selenoprotein M, and transferrin) were confirmed by quantitative RT-PCR, and their transcriptional changes in the livers of Java medaka induced by exposure to 10, 100, and $1000{\mu}g$/L $17{\beta}$-estradiol were investigated. These results should allow the development of biomarkers for the identification of $17{\beta}$-estradiol contamination in the environment and provide molecular biological information on the effects of endocrine-disrupting chemical exposure on marine animals.

        • SCIE

          The Zanthoxylum schinifolium seed oil modulates immune function under the biological safety level

          Seo, Joung-Wook,Park, Dae-Hun,Li, Yong-Chun,Kang, Hur-Je,Xu, Hong De,Kim, Young-Jin,Lee, Jong-Hwa,Lee, Myung-Sup,Lee, In Chul,Lee, Yun Lyul,Ahn, Jae-Bum,Cho, Soon-Chang,Lee, Min-Jae 대한독성유전단백체학회 2012 Molecular & cellular toxicology Vol.10 No.1

          Zanthoxylum schinifolium (Z. schinifolium) and the seed oil of Z. schinifolium has been widely used as culinary applications and traditional medicine for epigastric pain in Korea, China, and several Asia nations and the components or extracts of Z. schinifolium have been reported to have pharmaceutical effects such as anti-platelet aggregation, inhibitory activities against monoamine oxidase, antioxidant and anticancer activities, and anti-inflammatory activity. In this study we got the results that 200 mg/kg/day seed oil of Z. schinifolium oral administration for 13 weeks enhances most immune-related cells and is biologically safe. However as B cell population was increased by Z. schinifolium seed oil administration but B cell function was not changed by that, ultimately we deduced that Z. schinifolium seed oil doesn't have the modulation effect about B cell. To evaluate the biological safety of repeated Z. schinifolium seed oil administration the index of biological safety such as CBC, hematological enzymes, and especially histopathological morphologies was measured but no changes related with Z. schinifolium seed oil administration had been shown. Conclusively Z. schinifolium seed oil is one of the safe candidates to modulate immunity.

        • SCIE

          Identification of hepatotoxicity related genes induced by toxaphene in HepG2 cells

          Choi, Han-Saem,Kim, Youn-Jung,Song, Mee,Song, Mi-Kyung,Ryu, Jae-Chun 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.1

          Toxaphene is a bioaccumulative, persistent, and toxic pollutant. Toxaphene is one of the 12 priority of Persistent Organic Pollutants (POPs) intended for global action by the United Nations Environment Program (UNEP) Governing Council. POPs are manmade synthetic chemicals highly resistant to biodegradation, with a high affinity for bioaccumulation (due to their hydrophobic and/or lipophilic nature) and biomagnification in the environment and living organisms, including humans. Once deposited in humans (mainly in adipose tissue), they form stable compounds that result in a lasting toxic body burden. Most human populations are exposed to mixtures of POPs originated either from local or remote sources. Toxaphene is ubiquitous in air, water, soil, and biological matrices, as well as in major environmental compartments. Toxaphene has effects on various organs such as thyroid, bone, skin, kidneys, and blood cells and especially, revealed strong toxicity to liver. In this study, we identified genes related to hepatotoxiciy induced by toxaphene in human hepatocellular carcinoma (HepG2) cells using microarray and gene ontology (GO) analysis. Through microarray analysis, we identified 1,647 up- and 2,251 down-regulated genes changed by more than 1.5-fold and P-values 0.001 by toxaphene. And after GO analysis, we determined several key pathways which known as related to hepatotoxicity such as MAPK signaling pathway, complement and coagulation cascades, tight junction. Thus, our present study suggests that genes expressed by toxaphene may provide a clue for hepatotoxic mechanism of toxaphene.

        • SCIE

          Overexpression of SIRT2 contributes tumor cell growth in hepatocellular carcinomas

          Xie, Hong-Jian,Jung, Kwang-Hwa,Nam, Suk-Woo 대한독성유전단백체학회 2011 Molecular & cellular toxicology Vol.7 No.4

          The mammalian homolog of yeast Sir2 protein is the sirtuin family of histone deacetylases (HDACs), a NAD+-dependent protein deacetylase in humans. Accumulating evidence suggests that sirtuin 2 (SIRT2) co-localizes with the microtubule network and deacetylates ${\alpha}$-tubulin, and is involved in various cellular processes including calorie restriction-dependent life span extension, mitotic cell cycle regulation, cellular apoptosis, DNA damage repair, and genomic silencing. However, the underlying mechanisms of action remains poorly understood, especially in hepatocarcinogenesis. Hence in this study, to determine the association between the aberrant expression of SIRT2 and liver cancer development and progression, SIRT2 expression was investigated in ten selected hepatocellular carcinoma (HCC) tissues and matched normal liver tissues, using RT-PCR and Western blot analysis. Next, SIRT2 was disrupted by siRNA-mediated protein knockdown method to investigate the biological role of SIRT2 in hepatocarcinogenesis in Hep3B cells. As a result, we identified that SIRT2 expression was significantly up-regulated in HCC tissues compared to corresponding normal liver tissues. In addition, suppression of SIRT2 caused regression of tumor cell growth and proliferation. We also found that SIRT2 could interact with ${\alpha}$-tubulin and regulates the acetylation status of ${\alpha}$-tubulin in Hep3B cells. In conclusion, we suggest that SIRT2 is aberrantly regulated in HCCs which may contribute to the mitogenic potential of tumor cells during the development and progression of HCC, and could be a novel molecular target for therapeutic intervention in liver cancer.

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